Abiraterone and Ryzolt

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Abiraterone may alter the blood levels and effects of traMADol, and using these medications together can increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening, although it is a relatively rare side effect. You may be more susceptible if you have a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). Talk to your doctor if you have any questions or concerns. Your doctor may already be aware of the risks, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with these medications, whether together or alone. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

GENERALLY AVOID: Long-term androgen deprivation therapy with agents like abiraterone can prolong the QT interval. Tramadol may also prolong the QT interval, and theoretically, coadministration of multiple agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a randomized, active-controlled trial comparing the androgen deprivation agents degarelix and leuprolide, three patients (less than 1%) in the pooled degarelix group and four patients (2%) in the leuprolide 7.5 mg group had a Fridericia-corrected QT interval (QTcF) of 500 msec or greater. From baseline to end of study, the median change was 12.3 msec for degarelix and 16.7 msec for leuprolide. Investigators believe that long-term androgen deprivation is responsible for these changes, as testosterone has been found to shorten ventricular repolarization. The effect of tramadol on the QT interval was evaluated in a randomized, double-blind, 4-way crossover, placebo- and positive-controlled, multiple-dose ECG study of 62 healthy subjects. The maximum placebo-adjusted mean change from baseline in QTcF was 5.5 msec in the 400 mg/day treatment arm (100 mg every 6 hours on days 1 through 3 with a single 100 mg dose on day 4) and 6.5 msec in the 600 mg/day treatment arm (150 mg every 6 hours on days 1 through 3 with a single 150 mg dose on day 4), both occurring at the 8-hour time point. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MONITOR: Coadministration with abiraterone may decrease the opioid-like effects of tramadol, a substrate of the CYP450 2D6 isoenzyme. The mechanism is decreased conversion of tramadol to its active metabolite, M1, due to inhibition of CYP450 2D6 activity by abiraterone. In animal studies, M1 was up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in binding to mu-opioid receptors. When dextromethorphan, a CYP450 2D6 substrate, was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily, dextromethorphan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.8- and 2.9-fold, respectively, compared to administration alone.

MANAGEMENT: Concomitant use of abiraterone and tramadol should generally be avoided. If coadministration is required, careful consideration of the effects on tramadol and M1 is required. Patients should be monitored for opioid withdrawal, seizures, and serotonin syndrome, and care should be exercised in patients suspected to be at an increased risk of torsade de pointes. If abiraterone is discontinued, consider reducing the tramadol dose until stable drug effects are achieved and monitor for respiratory depression and sedation. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

Abiraterone

Generic Name: abiraterone

Brand name: Yonsa, Zytiga

Synonyms: Abiraterone Acetate

What is Abiraterone?

Ryzolt

Generic Name: tramadol

Brand name: ConZip, Rybix ODT, Ryzolt, Ultram, Ultram ER

Synonyms: n.a.

What is Ryzolt?